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Prospective meta-analysis of IL-1 gene complex polymorphisms confirms associations with ankylosing spondylitis.
  1. Anne-Marie Sims
  1. Diamantina Institute of Cancer, Immunology and Metabolic Medicine, University of Queensland, Australia
    1. Andrew E Timms
    1. Botnar Research Centre, University of Oxford, United Kingdom
      1. Jacome Bruges-Armas
      1. SEEBMO/The Azores, IBMC - Molecular and Cellular Biology Institute, University of Porto, Portugal
        1. Chung-Tei Chou
        1. Veterans General Hospital, Taipei, Taiwan
          1. Tracy Doan
          1. Diamantina Institute of Cancer, Immunology and Metabolic Medicine, University of Queensland, Australia
            1. Alison Dowling
            1. Diamantina Institute of Cancer, Immunology and Metabolic Medicine, University of Queensland, Australia
              1. Raquel N Fialho
              1. SEEBMO / The Azores, IBMC - Molecular and Cellular Biology Institute, University of Porto, Portugal
                1. Peter Gergely
                1. National Institute of Rheumatology and Physiotherapy, Budapest, Hungary
                  1. Dafna D Gladman
                  1. University of Toronto, Toronto, Ontario,, Canada
                    1. Robert Inman
                    1. University of Toronto, Toronto, Ontario,, Canada
                      1. Markku Kauppi
                      1. Rheumatism Foundation Hospital, Heinola, Finland
                        1. Kalevi Kaarela
                        1. Rheumatism Foundation Hospital, Heinola, Finland
                          1. Kari Laiho
                          1. Rheumatism Foundation Hospital, Heinola, Finland
                            1. Walter Maksymowych
                            1. University of Alberta, Alberta, Canad, Canada
                              1. Proton Rahman
                              1. Memorial University, Newfoundland,, Canada
                                1. John D Reveille
                                1. The University of Texas, Texas, United States
                                  1. Jaakko Tuomilehto
                                  1. National Public Health Institute, Helsinki, Finland
                                    1. B Paul Wordsworth
                                    1. Botnar Research Centre, University of Oxford, United Kingdom
                                      1. Huji Xu
                                      1. Changzheng Hospital, The Second Military Medical University, Shanghai, China
                                        1. Matthew A Brown (matt.brown{at}uq.edu.au)
                                        1. Diamantina Institute of Cancer, Immunology and Metabolic Medicine, University of Queensland, Australia

                                          Abstract

                                          Objectives: The aim of the current study is to determine the contribution of IL-1 gene cluster polymorphisms previously implicated in susceptibility to ankylosing spondylitis (AS), to AS susceptibility in different populations worldwide.

                                          Methods: Nine polymorphisms in the IL-1 gene cluster members IL1A (rs2856836, rs17561, and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL-1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel-Haenszel random effects analysis.

                                          Results: Strong association was observed with three SNPs in the IL1A gene (rs2856836, rs17561, rs1894399, P=0.0036, 0.000019, 0.0003 respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4-6%.

                                          Conclusions: This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL-1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.

                                          • ankylosing spondylitis
                                          • association
                                          • genetics
                                          • interleukin-1

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